Recent Advances on Therapeutic Approaches for Friedreich’s Ataxia: New Pharmacological Targets, Protein, and Gene Therapy

Friedreich ataxia (FA) is an inherited autosomal recessive neurodegenerative disorder. The most common mutation in FA is caused by a (GAA)n triplet repeat expansion in the first intron of the frataxin gene. However, in 4% of patients, the disease is caused by a compound heterozygous GAA expansion with a loss of function mutation on the other allele. The genetic defect results in low levels of frataxin, which is an essential gene for mitochondrial function. FA is a multisystemic disorder primarily characterized by progressive sensory and spinocerebellar ataxia. In addition to neurological symptoms, many FA individuals also present a hypertrophic cardiomyopathy and diabetes. In this chapter, we discuss recent therapeutic approaches, including a proof-of-concept study for gene therapy, drug development targeting the affected downstream pathways, paving the way for the first disease-modifying therapeutic approaches.